title: Effects of liver blood flow on the pharmacokinetics of tissue-type plasminogen activator (alteplase) during thrombolysis in patients with acute myocardial infarction.
abstract: BACKGROUND
  The removal of recombinant tissue-type plasminogen activator (rt-PA; alteplase) by the liver is so rapid that liver blood flow becomes rate determining for its clearance. In patients with myocardial infarction changes in liver blood flow may result from impaired cardiac performance or drug treatment.
  
  
  OBJECTIVE
  To estimate the effect of variations in liver blood flow on t-PA plasma concentrations during thrombolytic therapy.
  
  
  METHODS
  Fifteen patients with acute myocardial infarction were investigated in an open single-center study at the coronary care unit of University Hospital Leiden. Patients received thrombolytic treatment with 100 mg rt-PA over 3 hours. Liver blood flow was estimated by indocyanine green clearance and by Doppler echocardiography. Concentrations of t-PA antigen, t-PA activity, indocyanine green, alpha 2-antiplasmin, fibrinogen, and fibrin and fibrinogen degradation products were measured.
  
  
  RESULTS
  Indocyanine green clearance and clearance of both t-PA antigen (r = 0.78; p < 0:01) and t-PA activity (r = 0.54; p < 0.05) were significantly related. Significant associations between t-PA antigen and fibrin and fibrinogen degradation products and between t-PA antigen and alpha 2-antiplasmin were also found.
  
  
  CONCLUSIONS
  The liver blood flow of patients with myocardial infarction is inversely correlated with plasma concentrations of t-PA. In patients with severely impaired liver blood flow and heart failure, high t-PA plasma concentrations may occur if standard doses are given. This finding could contribute to optimization of the dosage of t-PA in certain patient groups.
authors.affiliation: Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: van Griensven
authors.forename: R W
authors.initials: RW
authors.lastname: Koster
authors.forename: J
authors.initials: J
authors.lastname: Burggraaf
authors.forename: L G
authors.initials: LG
authors.lastname: Huisman
authors.forename: C
authors.initials: C
authors.lastname: Kluft
authors.forename: R
authors.initials: R
authors.lastname: Kroon
authors.forename: R C
authors.initials: RC
authors.lastname: Schoemaker
authors.forename: A F
authors.initials: AF
authors.lastname: Cohen
mesh_terms: D000368:Aged; D004396:Coloring Agents; D015150:Echocardiography, Doppler; D005260:Female; D006801:Humans; D007208:Indocyanine Green; D008102:Liver Circulation; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D010960:Plasminogen Activators / Q000097:blood / Q000493:pharmacokinetics*; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D004396:Coloring Agents; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D007208:Indocyanine Green